Aging represents a major risk factor for prostate cancer; however, mechanisms responsible for this relationship remain unclear. Preclinical and some clinical investigations support the protective role of selenium against prostate cancer possibly through the reduction of oxidative stress. While increased levels of oxidative stress together with decreases in selenium and the major cellular antioxidant glutathione (GSH) are common in tissues of old animals, there is little data available on these parameters in the prostate. In the present study we have compared the levels of selenium, GSH and protein-bound GSH (GSSP) in blood and prostate tissues in young (4-month), mature (12-month), old (18 month), and very old (24 month) male F344 rats. Each prostate lobe (dorsolateral, DL; anterior, AL; ventral, VL) was analyzed separately based upon their differing potential for prostate cancer development. At all ages, selenium levels were lowest in DL < VL < AL. After 12 mo, an 85% reduction in selenium in the DL was observed (P < 0.05), while levels in other lobes were unchanged. In animals of all ages, levels of GSH were lowest in the VL < DL = AL and no significant changes were observed in GSH levels by 18 mo. However, GSSP, a marker of oxidative stress, was increased 90% after 18 mo in the DL only (P < 0.01). These findings of age-related changes in GSSP and selenium in the DL prostate are consistent with the sensitivity of this lobe to carcinogenesis and, thus, may be playing a mechanistic role.